Standard of Care Treatment for XLH

At a Glance

XLH treatment may use burosumab or conventional oral phosphate plus active vitamin D. Burosumab targets the excess FGF23 hormone, while conventional therapy replaces lost phosphate; the two approaches generally must not be combined and require careful monitoring for safety.

Treating X-Linked Hypophosphatemia (XLH) has historically focused on replacing what the body loses. However, newer treatments now target the underlying cause of the disease. The goal of any treatment is to improve bone health, reduce pain, and prevent long-term complications, though the approach often differs between children and adults ^[1]^[2].

🚨 CRITICAL MEDICATION SAFETY WARNING

Never mix Burosumab with Conventional Therapy. Oral phosphate and active vitamin-D analogues must generally NOT be co-administered with burosumab. Combining them carries a severe risk of hyperphosphatemia (dangerously high phosphate) and ectopic mineralization (calcium deposits in your organs).
Do not start, stop, combine, or change your doses on your own. A strict “washout” period and careful monitoring are required when switching treatments, according to local product labeling.

The Changing Treatment Landscape

For decades, the only option for XLH was conventional therapy. Today, a “disease-directed” therapy called burosumab is available. While conventional therapy replaces the missing phosphate, burosumab works by counteracting the hormonal imbalance that causes the phosphate loss in the first place ^[3]^[4].

Feature	Conventional Therapy	Burosumab (Crysvita)
Mechanism	Replaces phosphate and active Vitamin D ^[5]	Blocks excess FGF23 to counteract phosphate wasting ^[3]
Administration	Oral liquids or pills, multiple times per day ^[6]	Subcutaneous injection every 2 (kids) or 4 (adults) weeks ^[7]^[8]
Primary Goal	Heal rickets and improve growth ^[1]	Normalize phosphate levels and heal bone lesions ^[3]

Burosumab (Crysvita)

Burosumab is a monoclonal antibody, a type of protein designed to bind to a specific target in the body. In XLH, that target is the excess FGF23 hormone ^[3]. By neutralizing FGF23, burosumab allows the kidneys to reabsorb phosphate and helps the body produce its own active vitamin D ^[9].

For Children: International guidelines often recommend burosumab as a first-line treatment, especially for those with severe rickets or those who do not respond well to conventional therapy ^[10]^[11]. Studies show it is more effective than conventional therapy at healing rickets and improving height ^[12]^[13].
For Adults: Burosumab is strongly recommended for adults with pseudofractures or fractures that aren’t healing ^[1]. It has been shown to significantly improve the healing of these bone lesions compared to no treatment ^[8]. It may also be considered for symptomatic osteomalacia, pain, and impaired mobility depending on local guidelines and clinical evaluation.
Monitoring: Because burosumab is very effective, doctors must monitor for hyperphosphatemia (phosphate levels that are too high). If this happens, the dose may be lowered or paused temporarily ^[14]^[15]. If you miss a dose of burosumab, contact your prescribing team or infusion service immediately for product-specific rescheduling advice, and never double a dose.

Conventional Therapy

Conventional therapy involves taking oral phosphate supplements combined with an active form of vitamin D, such as calcitriol or alfacalcidol ^[5]^[1].

While this treatment can heal rickets and improve growth, it does not stop the body from “wasting” phosphate. Because the phosphate is quickly flushed out by the kidneys, it must be taken 3 to 5 times a day to maintain steady levels ^[6].

Risks and Complications

Conventional therapy requires a delicate balance. If the doses are too high or not balanced correctly, two main complications can occur:

Nephrocalcinosis: This is the buildup of calcium deposits in the kidneys. It happens due to treatment-associated hypercalciuria (excess calcium in the urine) and altered calcium/phosphate handling ^[16]^[17]. Regular renal (kidney) ultrasounds are needed to monitor for this ^[11].
Hyperparathyroidism: When the body takes in high doses of oral phosphate, the parathyroid glands may become overactive (secondary hyperparathyroidism). Over time, these glands can sometimes become autonomous (functioning on their own), which can actually make bone health worse ^[18]^[19].

Side Effects to Watch For

Every treatment carries risks. It is important to distinguish between expected side effects and those that require a change in plan.

Conventional Therapy Side Effects: The most common issue is gastrointestinal (GI) distress, including stomach pain, bloating, or diarrhea caused by the oral phosphate ^[20]^[3].
Burosumab Side Effects: The most frequent side effects are mild, such as injection-site reactions (redness or swelling where the shot was given), headache, or pain in the arms or legs ^[15]^[21]. Seek immediate care for any severe hypersensitivity reactions.

Regardless of the treatment chosen, your medical team will perform regular “biochemical monitoring.” This includes frequent blood and urine tests to ensure phosphate, calcium, and hormone levels stay within a safe and effective range ^[11]^[22]. Areas of focus usually include your alkaline phosphatase (ALP) levels, which help track how well your bones are mineralizing ^[23]^[24].

Common questions in this guide

What treatments are used for X-linked hypophosphatemia?

XLH may be treated with burosumab, which blocks the excess FGF23 hormone, or with conventional therapy using oral phosphate plus active vitamin D such as calcitriol or alfacalcidol. The choice depends on age, symptoms, rickets or bone lesions, treatment response, and local guidance.

Is burosumab better than phosphate and vitamin D for children with XLH?

Burosumab is often recommended first for children with severe rickets or a poor response to conventional therapy. Studies show that it can heal rickets and improve height more effectively than conventional therapy, but the child's clinician should select treatment based on individual needs and local guidance.

Can I take burosumab with phosphate or active vitamin D?

Generally, no. Oral phosphate and active vitamin D medicines should not usually be taken with burosumab because combining them can cause dangerously high phosphate levels and calcium deposits in organs. A prescribed washout period and blood monitoring are needed when switching, so never combine or change these medicines without guidance from the treating team.

How is burosumab given, and what should I do if I miss a dose?

Burosumab is given as an injection under the skin, usually every 2 weeks in children and every 4 weeks in adults. If you miss a dose, contact your prescribing team or infusion service for product-specific rescheduling advice, and do not double the next dose.

What are the risks of conventional XLH treatment?

Oral phosphate and active vitamin D can cause stomach pain, bloating, or diarrhea. If doses are too high or poorly balanced, treatment can also contribute to calcium deposits in the kidneys or overactive parathyroid glands, so regular blood, urine, and kidney ultrasound monitoring is important.

How will my XLH treatment be monitored?

Your care team may use blood and urine tests to check phosphate, calcium, parathyroid hormone, and alkaline phosphatase, which helps show how bones are mineralizing. Kidney ultrasounds may be used during conventional therapy to look for calcium deposits, and burosumab may be lowered or paused if phosphate becomes too high.

When might an adult with XLH receive burosumab?

Burosumab is strongly recommended for adults with pseudofractures, which are cracks in weakened bone, or fractures that are not healing. Depending on local guidance and clinical evaluation, it may also be considered for symptomatic osteomalacia, pain, or impaired mobility; adults without current pseudofractures need an individualized treatment decision.

Curated prompts to bring to your next appointment.

1.Based on my (or my child’s) rickets severity and symptoms, is burosumab recommended over conventional therapy?
2.How will we monitor for hyperparathyroidism or nephrocalcinosis, and how often will I need renal ultrasounds?
3.What is the target for our treatment? Are we aiming to normalize my phosphate levels or my alkaline phosphatase (ALP) levels?
4.If I (or my child) experience a skin reaction at the injection site, what is the best way to manage it at home?
5.Since I am an adult, does my lack of current pseudofractures change whether I should start burosumab or stay on conventional therapy?

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

Key takeaways

Burosumab blocks excess FGF23 and helps the kidneys retain phosphate, while conventional therapy replaces phosphate with oral supplements and active vitamin D.
Burosumab is often first-line for children with severe rickets or poor response to conventional therapy and is strongly recommended for adults with pseudofractures or fractures that are not healing.
Oral phosphate and active vitamin D generally must not be combined with burosumab because the combination can cause dangerously high phosphate and calcium deposits in organs.
XLH treatment requires regular blood and urine testing, and conventional therapy may also require kidney ultrasounds to check for nephrocalcinosis.
Common side effects include gastrointestinal symptoms with phosphate and injection-site reactions, headache, or limb pain with burosumab.

References (24)

1
X-Linked Hypophosphatemia Management in Adults: An International Working Group Clinical Practice Guideline.
Khan AA, Ali DS, Appelman-Dijkstra NM, et al.
The Journal of clinical endocrinology and metabolism 2025; (110(8)):2353-2370 doi:10.1210/clinem/dgaf170.
PMID: 40243526
2
Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.
Haffner D, Emma F, Seefried L, et al.
Nature reviews. Nephrology 2025; (21(5)):330-354 doi:10.1038/s41581-024-00926-x.
PMID: 39814982
3
Phosphatonins: From Discovery to Therapeutics.
Kritmetapak K, Kumar R
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 2023; (29(1)):69-79 doi:10.1016/j.eprac.2022.09.007.
PMID: 36210014
4
FGF23 and Associated Disorders of Phosphate Wasting.
Gohil A, Imel EA
Pediatric endocrinology reviews : PER 2019; (17(1)):17-34 doi:10.17458/per.vol17.2019.gi.fgf23anddisordersphosphate.
PMID: 31599133
5
Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia.
Trombetti A, Al-Daghri N, Brandi ML, et al.
Nature reviews. Endocrinology 2022; (18(6)):366-384 doi:10.1038/s41574-022-00662-x.
PMID: 35484227
6
Clinical guidelines for burosumab in the treatment of XLH in children and adolescents: British paediatric and adolescent bone group recommendations.
Padidela R, Cheung MS, Saraff V, Dharmaraj P
Endocrine connections 2020; (9(10)):1051-1056.
PMID: 33112809
7
Safety and Efficacy of Burosumab in Pediatric Patients With X-Linked Hypophosphatemia: A Phase 3/4 Open-Label Trial.
Namba N, Kubota T, Muroya K, et al.
Journal of the Endocrine Society 2022; (6(5)):bvac021 doi:10.1210/jendso/bvac021.
PMID: 35356008
8
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis.
Insogna KL, Briot K, Imel EA, et al.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2018; (33(8)):1383-1393 doi:10.1002/jbmr.3475.
PMID: 29947083
9
Burosumab in X-linked hypophosphatemia: a profile of its use in the USA.
Lyseng-Williamson KA
Drugs & therapy perspectives : for rational drug selection and use 2018; (34(11)):497-506 doi:10.1007/s40267-018-0560-9.
PMID: 30459508
10
Diagnosis, treatment-monitoring and follow-up of children and adolescents with X-linked hypophosphatemia (XLH).
Rothenbuhler A, Schnabel D, Högler W, Linglart A
Metabolism: clinical and experimental 2020; (103S()):153892 doi:10.1016/j.metabol.2019.03.009.
PMID: 30928313
11
Burosumab for X-linked hypophosphatemia in children and adolescents: Opinion based on early experience in seven European countries.
Mughal MZ, Baroncelli GI, de Lucas-Collantes C, et al.
Frontiers in endocrinology 2022; (13()):1034580 doi:10.3389/fendo.2022.1034580.
PMID: 36798486
12
Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial.
Imel EA, Glorieux FH, Whyte MP, et al.
Lancet (London, England) 2019; (393(10189)):2416-2427 doi:10.1016/S0140-6736(19)30654-3.
PMID: 31104833
13
Burosumab vs Phosphate/Active Vitamin D in Pediatric X-Linked Hypophosphatemia: A Subgroup Analysis by Dose Level.
Imel EA, Glorieux FH, Whyte MP, et al.
The Journal of clinical endocrinology and metabolism 2023; (108(11)):2990-2998 doi:10.1210/clinem/dgad230.
PMID: 37084401
14
Real-world effectiveness of burosumab in children with X-linked hypophosphatemic rickets.
Paloian NJ, Nemeth B, Sharafinski M, et al.
Pediatric nephrology (Berlin, Germany) 2022; (37(11)):2667-2677 doi:10.1007/s00467-022-05484-7.
PMID: 35211790
15
Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney.
Kumar S, Girgis CM, Tran B, et al.
JBMR plus 2025; (9(Suppl 5)):v39-v46 doi:10.1093/jbmrpl/ziae132.
PMID: 41445548
16
Nephrocalcinosis and Nephrolithiasis in X-Linked Hypophosphatemic Rickets: Diagnostic Imaging and Risk Factors.
Colares Neto GP, Ide Yamauchi F, Hueb Baroni R, et al.
Journal of the Endocrine Society 2019; (3(5)):1053-1061 doi:10.1210/js.2018-00338.
PMID: 31065622
17
Switching from conventional therapy to burosumab injection has the potential to prevent nephrocalcinosis in patients with X-linked hypophosphatemic rickets.
Harada D, Ueyama K, Oriyama K, et al.
Journal of pediatric endocrinology & metabolism : JPEM 2021; (34(6)):791-798 doi:10.1515/jpem-2020-0734.
PMID: 33837680
18
Hyperparathyroidism and parathyroidectomy in X-linked hypophosphatemia patients.
DeLacey S, Liu Z, Broyles A, et al.
Bone 2019; (127()):386-392 doi:10.1016/j.bone.2019.06.025.
PMID: 31276850
19
Secondary and Tertiary Hyperparathyroidism among Patients with X-Linked Hypophosphatemia: A Systematic Review and Meta-analysis.
Fisch SA, Zilberman S, Tudor A, et al.
Calcified tissue international 2025; (117(1)):4 doi:10.1007/s00223-025-01468-5.
PMID: 41437161
20
Complications of Phosphate and Vitamin D Treatment in X-Linked Hypophosphataemia.
Arango Sancho P
Advances in therapy 2020; (37(Suppl 2)):105-112 doi:10.1007/s12325-019-01170-7.
PMID: 32236871
21
Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia.
Linglart A, Imel EA, Whyte MP, et al.
The Journal of clinical endocrinology and metabolism 2022; (107(3)):813-824 doi:10.1210/clinem/dgab729.
PMID: 34636899
22
Postprandial serum phosphorus and calcium concentrations in adults and children with X-linked hypophosphatemia during burosumab treatment.
Portale AA, Jan de Beur SM, Munns CF, et al.
JBMR plus 2026; (10(4)):ziag008 doi:10.1093/jbmrpl/ziag008.
PMID: 41777640
23
Burosumab in management of X-linked hypophosphataemia: a retrospective cohort study of growth and serum phosphate levels.
Walker EYX, Lindsay TAJ, Allgrove J, et al.
Archives of disease in childhood 2023; (108(5)):379-384 doi:10.1136/archdischild-2022-324962.
PMID: 36717209
24
Effects of Burosumab Treatment on Mineral Metabolism in Children and Adolescents With X-linked Hypophosphatemia.
Ewert A, Rehberg M, Schlingmann KP, et al.
The Journal of clinical endocrinology and metabolism 2023; (108(10)):e998-e1006 doi:10.1210/clinem/dgad223.
PMID: 37097907

This page is for informational purposes only and does not constitute medical advice. Your XLH care team should guide treatment choices, medication changes, washout periods, and safety monitoring.

Get notified when new evidence is published on X-linked hypophosphatemia.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

Guide Contents